We propose to continue our investigations into a) The biochemical and structural components of surface membranes in normal human and familial hypercholesterolemic fibroblasts in culture, and b) The mechanisms of interaction of porcine lipoproteins with both pig liver membranes and fibroblasts in culture. The three major glycoproteins from the surface membranes of normal human fibroblasts will be isolated, characterized and their binding with plasma lipoproteins studied. The kinetics of binding of highly purified porcine liver membranes with pig native and enzymatically modified lipoproteins is under study to better understand the mechanisms of lipoprotein-cell membrane interaction. These studies will also be performed in pig fibroblasts in culture. This research may provide a greater understanding of the basic molecular defect in familial hypercholesterolemia and the biochemical mechanism(s) of lipoprotein binding. The information gained in these areas may prove useful in understanding the pathophysiology of atherosclerosis.